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147

31. Köpke S, Mühlhauser I, Gerlach A etal (2012) Effect of a guideline-based multicomponent

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venting falls and injuries of home-dwelling older adults: a randomised controlled trial. Injury

45:265–271

15 Fall Prevention

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149

J.-P. Michel (ed.), Prevention of Chronic Diseases and Age-Related Disability,

Practical Issues in Geriatrics, https://doi.org/10.1007/978-3-319-96529-1_16

J. Flamaing

Department of Geriatric Medicine, UZ Leuven, Leuven, Belgium

Division of Gerontology and Geriatrics, Department of Chronic Diseases, Metabolism, and

Ageing (CHROMETA), KU Leuven, Leuven, Belgium

e-mail: johan.amaing@uzleuven.be

Promotion ofaLifelong Immunization

Program forHealthy Ageing

JohanFlamaing

Key Messages

• Adult vaccination is often neglected in midlife.

• Later in life, multimorbidity, frailty, malnutrition, and immunosenescence

increase the risk of vaccine preventable diseases.

• Due to worldwide vaccination, tetanus and diphtheria became rare diseases. In

Europe, tetanus and diphtheria affect mainly older adults with a high mortality

rate.

• Pertussis is a frequent disease in adults (parents and grandparents), with regular

transmission to children.

• Excess winter mortality in persons 65+ can be attributed to inuenza and low

vaccine coverages in this target population and their (in)formal caregivers.

• The mortality rate of invasive pneumococcal disease is highest in older persons

and 60 times higher for persons 85+ than for children.

• The incidence of shingles and postherpetic neuralgia increases with age with a

subsequent negative impact on quality of life.

• There is a suboptimal protection against these vaccine preventable diseases

(VPDs).

• A lifelong vaccination strategy that directly (vaccination and boosting) and indi-

rectly (herd protection) protects against VPD is the best option to optimally pro-

tect older adults.

• Vaccine providers and the healthcare system must coordinate their efforts to

increase vaccine uptake from birth till old age.

https://t.me/med1917

150

16.1 Introduction

The burden of infectious diseases is spread throughout life but young children and

older adults mostly have the highest incidence, morbidity, and mortality caused by

infections.

In infants immunity needs to be acquired to cope with infections later in life and

in many countries immunization against vaccine preventable diseases (VPDs) is

embedded in national childhood vaccination programs supported by the healthcare

system, GPs, child care and school prevention programs.

For adults, unless there is an occupational hazard for a VPD with an associated

prevention program in the workplace, the individual person is often responsible for

his/her immunization.

In the older age group, a complex and heterogeneous population regarding mul-

timorbidity, frailty, cognitive and physical function, and nutritional status, the risk

and consequences of VPD are most pronounced but a structured approach to VPD

prevention in this population is often lacking.

In this chapter, the rationale and impact of a lifelong vaccination program that

helps attaining the goal of “healthy ageing” is discussed.

16.2 Vaccine Preventable Disease Epidemiology

inOlder Persons

The incidence and impact (morbidity, mortality) of relevant VPD that affect (older)

adults are summarized in this section.

16.2.1 Tetanus

With an estimated global Tetanus-diphtheria (Td) vaccination coverage of nearly

90%, tetanus has become a rare disease with 13,502 reported cases worldwide in

2016. Neonatal tetanus is estimated to cause the death of 61,000 newborns yearly

(2011) mainly in rural areas with poor perinatal hygiene [1]. In developed countries,

where tetanus has become a rare disease, its incidence is highest in the older popula-

tion, increases with advancing age and mortality is ve times higher than in the popu-

lation under 65years reaching a mortality rate of 50% for persons over 80years [2].

This higher incidence in older persons is correlated with a lower vaccine cover-

age in the population over 65years (50% in the article referred) and the lack of

protective levels of antibodies in about 70% of persons 70years or older [3].

16.2.2 Diphtheria

Due to the combined vaccination against tetanus and diphtheria, the latter VPD has

also become rare with 7079 cases reported globally in 2016 [4]. In the EU, 35 cases

were reported in 2014 (22 C. diphtheriae and 13 C. ulcerans cases). Diphtheria

J. Flamaing

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151

occurred in every age groups, 11% in persons 65years or older and one lethal case

occurred in an 88years old woman. Vaccination coverage in the diphtheria cases

was only 50%. A lack of protective diphtheria antitoxin immunoglobulins has been

shown in up to 70% of the older population [5].

16.2.3 Pertussis

An increasing incidence of pertussis is reported worldwide (2016: 139,535 reported

cases) and in the EU (40,727 cases in 2014, a 2.5-fold increase compared to 2000).

Waning immunity, awareness, and better diagnostics can explain this increase [6].

Vaccination strategies for pertussis: vaccination of newborns, infants, children,

healthcare workers (HCW), pregnant women, adults, and cocoon vaccination aim to

protect young infants, while disease burden in the (older) adult population is under-

estimated due to an often asymptomatic or mild course.

However, passive surveillance and outbreak data suggest that up to 58% of per-

tussis cases occur in persons 60years or older resulting in hospitalizations with a

longer length of stay (LOS) and deaths (often by cerebral hemorrhage) [7].

In pertussis cases, 44% are un- or under vaccinated [6]. Only 22% of persons

65years or older reported being vaccinated against pertussis the last 10years in the

USA [8]. Protective immunity against pertussis wanes after 5–10years. Although

no good correlate for protection exists for pertussis, 1/3 adults had no detectable

antibodies against pertussis despite childhood vaccination in an Australian and

Belgian population, suggesting susceptibility to the disease [9].

16.2.4 Influenza

The yearly inuenza epidemics result in a disproportionally high burden of disease

in older persons with great inter-seasonal variation depending on the circulating

inuenza strain (with a higher burden in older persons for H3N2>H1N1>B).

While the rates of inuenza-related GP visits are not highest in the older popula-

tion (the highest rate of GP visits is in children), the rates for inuenza-related

hospitalizations, ICU admissions and deaths are. In the older population the pres-

ence of chronic conditions more than doubles the inuenza-related hospitalization

rate, while mortality is comparable with or without risk condition (chronic obstruc-

tive respiratory disease, cardiovascular, central nervous system, renal and liver dis-

orders, diabetes, immunosuppressive conditions, or stroke) [10]. In Europe, 88% of

the excess winter mortality in persons 65years or older could be attributed to the

H3N2 epidemic in 2016–2017 [11].

Although vaccination against inuenza is recommended for older persons and

persons at risk in most European countries, the EU goal of 75% coverage of the

target population was only reached in three countries for the season 2012–2013

(The Netherlands, UK Northern Ireland, and UK Scotland) [12]. Decreasing trends

in inuenza vaccine coverage are documented in several countries (Belgium and

Italy) [13, 14].

16 Promotion ofaLifelong Immunization Program forHealthy Ageing

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152

16.2.5 Pneumococcal Disease

While the incidence of (invasive) pneumococcal disease (IPD) is highest in chil-

dren, mortality of IPD is concentrated in older persons. With an overall mortality

rate of 1/100,000, the IPD mortality in persons 85years or older (11.56/100,000) is

nearly 60 times higher than in children (0.2/100,000). Every decade after the age of

50, the mortality rate of IPD doubles from 1.5/100,000 for the age group 50–64 to

the mortality rate for persons 85years or older mentioned above [15].

WHO does not prioritize adult pneumococcal vaccination [16]. Pneumococcal

vaccination of older adults, although recommended in the majority of European coun-

tries and the USA, is not well established in most of these countries. The best PPV23

uptake is documented in England with an uptake of 70% in persons 65years or older

and reaching just over 80% in persons 75years or older [17]. Vaccination with PPV23,

PCV 13, or both vaccines was only reported by 43%, 31.5%, and 18.3% of Medicare

beneciaries belonging to the target group for pneumococcal vaccination, respec-

tively, despite the Advisory Committee on Immunization Practices (ACIP, USA) rec-

ommendation to use both vaccines sequentially [18]. In Belgium, only 12.5% of

persons 75years of age reported being vaccinated with a decreasing trend over time

and the Netherlands does not recommend pneumococcal vaccination in adults [14].

16.2.6 Herpes Zoster (HZ)

The incidence of herpes zoster increases with age and is four times higher in per-

sons 95 years and older (9.45/1000 person years) than in persons of 40 years

(2.15/1000 person years. Mainly hospitalization-based diagnoses for HZ increase

substantially with advancing age (with a factor 10 between 40 and 90years (0.1 to

1.1/1000 person years). Sixty percent of HZ diagnoses are made in women and

depending upon the severity, immunosuppression can double HZ incidence rates

[19]. Due to population ageing and extended life expectancy, a 100–300% increase

of HZ cases is expected depending on the country’s demography. The incidence of

postherpetic neuralgia, the most common complication of HZ infection, and its

duration, also increases with age. Postherpetic neuralgia (PHN) has an impact on

the quality of life in all health domains [20].

Vaccination against HZ and PHN is recommended since 2008in the USA and in

the UK since 2010. In the USA, 31% of persons 65years or older were vaccinated

against HZ in 2014 and in the UK 55% of persons 70 or 78years of age were vac-

cinated in 2015, but the vaccination coverage was dropping compared to previous

years [8]. Other countries (Germany, France, Belgium) also developed guidelines

for vaccination against HZ but data on vaccine uptake are lacking.

All these data demonstrate the high burden of and suboptimal protection against

VPD in the (older) adult population. In persons 65years or over more than 5, 2 mil-

lion VPD (Inuenza, Pneumococcal disease, Herpes Zoster, and Pertussis) cases

occurred with an associated cost of more than 15billion dollars in 2015in the USA

[21]. Even highly developed countries struggle to obtain a high vaccine uptake in

older adults.

J. Flamaing

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153

16.3 The Impact ofFrailty, Immunosenescence,

andComorbidity onVaccine Effect

Immunosenescence is the decline in systemic immunity associated with ageing and

involves both innate and adaptive immune responses. Oligoclonal accumulation of

senescent T-lymphocytes stimulated by latent (herpes) viruses with less naïve

T-lymphocytes to combat new infections is a key feature in immunosenescence of the

adaptive immune system. Therefore older adults are more susceptible to VPD that

tend to be more severe than in younger people. Immunosenescence also impairs the

capacity to respond to a vaccine with lower vaccine effectiveness as a consequence.

While the primary immune response is blunted in older persons, the recall or booster

response seems to be intact [22]. The elderly population is extremely heterogeneous

with a variety of underlying medical conditions, medications, nutritional, functional

and cognitive status, previous infections, and environmental exposures. In this com-

plex phenotype, the isolation of the contribution of immunosenescence to VPD sus-

ceptibility and vaccine (in)effectiveness is difcult. In carefully selected healthy older

persons, the immune responses to vaccines are comparable to younger adults. The

correlation between the frailty syndrome, immunosenescence, and vaccine response/

effect needs clarication, as immune response and effectiveness studies comparing

frail, prefail, and t older persons give conicting results [23, 24].

16.3.1 Pneumococcal Vaccines

In contrast to the 2013 Cochrane review concluding that in high-risk elderly and

adults with underlying conditions the 23-valent pneumococcal polysaccharide vac-

cine (PPV23) does not offer protection against pneumococcal disease, recent meta-

analyses show that PPV23 protects against both invasive pneumococcal disease and

pneumococcal pneumonia [25]. The 13-valent pneumococcal conjugate vaccine

(PCV13) protects older adults with underlying conditions against IPD and pneumo-

coccal pneumonia caused by PCV13 serotypes with an age dependent decline (VE

65% to VE 40% between 65 and 75years) up to the age of 80years [26]. PCV13

induces a boostable immune-memory with comparable or higher secondary sero-

type-specic antibodies. Combining the effectiveness of PCV13 and broad cover-

age of PPV23 may offer older adults the best protection against pneumococcal

disease (pneumococcal pneumonia and invasive disease).

16.3.2 Influenza Vaccine

Older persons are able to mount protective levels of antibodies against inuenza

virus. No difference in seroprotection was found between institutionalized persons

60–85years and persons >85years in an analysis of immunogenicity data over 21

seasons in Italy for 2 of the 3 strains (except B) in the trivalent inactivated inuenza

vaccine (TIV). Women, new antigens and enhanced (adjuvanted or intradermally

(ID)) vaccines mounted a better response irrespective of age [27].

16 Promotion ofaLifelong Immunization Program forHealthy Ageing

https://t.me/med1917

154

Controversy on the protective effect of TIV in the elderly persists and is mainly

caused by the lack of adequately powered RCTs in this population and the biases

present in observational studies where different inclusion criteria, settings, and out-

comes are reported. However, recent studies show that TIV prevents lab conrmed

inuenza (VE: 42–54%), hospitalizations (VE: 40–47%), and mortality (VE: 16%,

NNV: 65–74years: 649, ≥75years: 251) in older persons and that the level of pro-

tection is inuenced by age, comorbid conditions, and inuenza type (protection

against H1N1>B>H3N2) [28, 29].

16.3.3 Herpes Zoster Vaccine (VZV)

The live-attenuated VZV reduces the overall incidence of VZ (VE: 51.3%), PHN

(VE: 66.5%), and the burden of illness (BOI) related to VZ (VE: 61.1%). These

effects are age and time dependent. In higher age groups, the VE on HZ incidence

is less (60–69years: 64%, 70–79years: 41%), and no signicant VE was present in

persons 80years or older. This age dependent VE decline was not demonstrated for

PHN and BOI but data on VE ≥ 80 years were not available in the Shingles

Prevention Study (SPS). The VE also wanes over time. In long-term follow-up stud-

ies of the SPS (up to 11years after vaccination), a decline in VE for HZ incidence

(VE: 51.3% to 31.1% in year 8 of FU), BOI (VE: 61.1% to 33.3% in year 10 of FU),

and PHN (VE: 66.5% to 35.4%) was noticed. Whether revaccination could be ben-

ecial needs further evaluation [30].

An inactivated adjuvanted subunit VZV in a 2 dose schedule demonstrated a VE

of ±90% on the incidence of HZ and PHN even in persons ≥80years. FDA/EMA

approval for this vaccine has been obtained [31].

16.3.4 Tetanus, Diphtheria, andPertussis (Tdap) Vaccine

The level of antibodies protective against tetanus, diphtheria, and pertussis wane

over time. Booster vaccination is recommended every 10 years. Older persons

≥65years mount a good booster antibody response against tetanus (94.5% seropro-

tection), diphtheria (82.8% seroprotection), and pertussis antigens (±90% seropro-

tection depending on the antigen) [32].

There are no trials on the effectiveness of Tdap vaccination in older persons

because high coverage rates have made clinical VPD rare (see section on epidemiol-

ogy of tetanus, diphtheria, and pertussis).

16.4 Strategies toAugment Protection ofOlder Persons

Against VPD

Enhanced protection of older persons against VPD can be achieved by the use of

more efcient vaccines, vaccination strategies, and vaccine implementation.

J. Flamaing

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155

16.4.1 Augmenting theVaccine Effect

As immune-rejuvenation to combat immunosenescence is at this moment not pos-

sible, the use of more immunogenic vaccine formulations in older persons is a good

choice to better protect older persons against VPD.

Vaccines that induce a higher immune response (and possibly better protection

against VPD) are to be preferred in older persons. For this purpose, higher doses of

antigens in vaccines (e.g., TIV), adjuvanted vaccines (e.g., MF59 adjuvanted TIV,

adjuvanted VZV), specic vaccine formulations (e.g., virosomal vs. split virus inac-

tivated TIV, pneumococcal conjugate vs. polysaccharide vaccine, live-attenuated vs.

conjugated HZV), and applications (e.g., intradermal vs. sc TIV) induce higher pro-

tective antibody levels.

Vaccines must protect against circulating epidemic strains and adaptation of vac-

cine formulations is often necessary. Yearly adaptation of inuenza vaccines with

broader coverage (e.g., QIV (H1N1, H3N2, B Yamagata, and B Victoria) vs. TIV

(without B Victoria) will have higher protective potential depending on the circulat-

ing strains of inuenza. A mismatch can lead to higher inuenza related disease

burden and mortality. Including more (prevalent) pneumococcal serotypes in pneu-

mococcal vaccines will broaden the protection against pneumococcal disease (PCV

7—PCV 13—PPV 23).

Boosting immune-memory after priming vaccination can maintain antibodies

and protection against VPD.Repeat vaccination is necessary to protect against teta-

nus, diphtheria, pertussis, and inuenza. Using the pneumococcal polysaccharide or

conjugate vaccine after priming with the pneumococcal conjugate vaccine induces

a booster response. Whether repeat vaccination over time with pneumococcal and

HZ vaccines is benecial is not clearly established [33].

16.4.2 Vaccination Strategies

Age-based vaccination (childhood vaccination program, vaccination of persons

60–65 years or older), occupational vaccination (HCW, occupational exposition

(e.g., poultry farmers)), and risk-based vaccination (for chronic diseases and/or

immunocompromising conditions) are strategies that aim at protecting susceptible

persons directly against VPD.

While the strategies mentioned above augment direct protection, an indirect pro-

tection of older persons against VPD can be obtained by vaccinating the population

serving as an important reservoir and/or vector for VPD.Persons lacking protection

against VPD have a lower chance contracting a VPD when most of the population

susceptible to the VPD is vaccinated (herd protection). Vaccinating children (and

adults) against inuenza protects the older population against inuenza and inu-

enza-related hospitalization and mortality. This resulted in the recommendation to

vaccinate all citizens in the USA against inuenza [34]. Vaccination of children

against pneumococcal disease resulted in a signicant decline of the incidence and

mortality caused by invasive pneumococcal disease in the USA in the older

16 Promotion ofaLifelong Immunization Program forHealthy Ageing

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156

population as well (Fig.16.1, [15]). Vaccination against pertussis should be main-

tained throughout life (cocoon vaccination) not only for direct protection, but also

to reduce transmission to the very young and very old.

Caregivers and HCWs in contact with older persons can protect themselves

against VPD (hepatitis A and B, inuenza, tetanus, diphtheria, and pertussis).

Additionally transmission of VPD from themselves towards susceptible persons is

prevented.

Taking all these considerations together vaccination should be considered as

a tool to prevent VPD throughout life and not only for certain age- or risk-

groups. A lifelong vaccination program incorporating direct (priming and boost-

ing vaccination) and indirect (herd) protection against VPD in a lifelong

vaccination program is the best strategy to obtain (VPD free) healthy ageing. As

an example, the scheme of Italian lifelong vaccination program is shown in

Fig.16.2 [35].

16.4.3 Vaccine Implementation

Despite the high burden of VPD in (older) adults and the availability of effective

vaccines, the vaccine uptake in this population is often very low in many countries

(cf. VPD epidemiology section of this article).

: 1998

11,02

4,02

6,12

: 2015

< 112-45-17

Age Group

VPD in older persons IPD case fatality, USA

Case fatality / 100,000

18-34 35-49 50-64 ≥

0,24

Fig. 16.1 Case fatality of invasive pneumococcal disease in the USA 1998 vs. 2015. VPD vaccine

preventable disease, IPD invasive pneumococcal disease

J. Flamaing

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157

There are three parties involved in the implementation of vaccination: the vac-

cine recipient, the vaccine provider, and the healthcare system.

Active recommendation to be vaccinated by the primary healthcare profes-

sional is the most important factor that enhances vaccine uptake in the recipi-

ent besides awareness of personal disease risk for VPD, safety of vaccination,

accessibility, and cost of vaccination. Household, family members and direc-

tives from healthcare institutions recommending vaccination support individual

vaccination.

The knowledge of VPD and vaccine effects and positive (pay per performance)

and/or negative (penalty/control via a vaccination threshold) incentives to vaccinate

are the factors driving the vaccine providers willingness to vaccinate.

The healthcare system can, at different levels, do VPD surveillance, issue vacci-

nation guidelines, raise awareness and knowledge of VPD and vaccination in recipi-

ents and providers, reimburse vaccine costs for recipients, and give incentives to

providers.

There is a complex interplay between these three stakeholders and a multicom-

ponent coordinated intervention framework is needed to have an impact on vaccine

uptake (Fig.16.3, [36]).

Vaccino

DTPa** DTPa**

dTpalPV

(1)

(2)

(3)

(4) ^^PCV+PPSV

MPRV MPRV

oppure

MPR

Men C

Men ACWY

coniugato

MPR

oppure

(6) ^

(6)^

(7)

(8)

1 dose

all'anno

1 dose# (10)

(11)

(9)°°

(5)*****

1 dose dTpa**** ogni 10 anni

DTPa DTPa DTPa

0gg-30gg

EpB-EpB*

3°

mese mese mese mese mese mese mese mese anno anno anni anni

Soggetti ad

anumentato

rischio

4° 5° 6° 7° 11° 13° 15° 6° 12°-18° 19-49 50-64

> 64 anni

IPVIPV

Ep B Ep B Ep B

IPVIPV IPV

Epatite B

HibHib

PCV PCV PCV

HibHib

Pneumococco

MPRV

MPR

Varicella

Meningococco C

Men BMen BMen BMen B

Rotavirus## (due o tre dosi

a seconda del tipo di vaccino)

HPV°: 2-3 dosi (in

funzione di età e vaccino)

Meningococco B*^

HPV

Influenza

Herpes Zoster

Rotavirus

Epatite A

II calendario vaccinale del Piano Nazionale di Prevenzione Vaccinale 2017-2019

Fig. 16.2 National lifelong vaccination calendar, Italy 2017–2019. Vaccine abbreviations not

translated from Italian

16 Promotion ofaLifelong Immunization Program forHealthy Ageing

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